We propose to prospectively study four major hypotheses which may explain regional variations in breast cancer incidence in the U.S. These hypotheses are: 1. That levels of DDE (a metabolite of DDT) and PCBs are higher in stored blood specimens from women who develop breast cancer compared with women who do not develop breast cancer. 2. That some or all of the regional differences in breast cancer incidence in a large multi-state cohort can be explained by regional differences in prevalence of reproductive and dietary risk factors. 3. That high exposure to electromagnetic fields, specifically regular sleeping on an electric blanket, is associated with increased risk of breast cancer. 4. That vitamin D levels in the stored blood of women who develop breast cancer are lower than in women who do not. To accomplish this we will utilize prospective data from 121,700 women followed since 1976 in the Nurses' Health Study, and perform nested case- control studies based in the cohort of 33,000 women from whom we obtained a blood sample In 1989-90. We will analyze levels of DDE and PCB's among 430 women expected to develop breast cancer after giving us a blood sample and before June 1,1996, and compare these with these levels among 430 controls matched on year of birth and month of blood return. Similarly, we will analyze these specimens for 25-Hydroxyvitamin D, the major circulating metabolite of vitamin D. In 1992 we enquired about electric blanket use, an important source of exposure to EMF, and implicated in breast cancer etiology in a previous case-control study, and we will study this exposure prospectively. In four years of follow-up we expect 1,652 cases to occur which will give us ample power to examine this issue. We will study regional variations in the incidence and mortality of breast cancer prospectively from the start of the study in 1976. We will examine the prevalence of specific risk factors, including screening behavior, in each region, and control for these risk factors to assess the extent to which they explain regional variations in incidence and mortality.